Glycans are sugar structures found attached to cells and proteins throughout the body. These carbohydrate chains play diverse roles in biological systems, acting as a form of cellular communication and recognition. Among the many types of glycans, g0f glycan is a widely studied example due to its pervasive presence and involvement in various physiological and pathological processes, influencing normal bodily functions and disease progression.
Understanding g0f Glycan
G0F glycan, also known as NGA2F, is an asialo-, agalacto-, core-fucosylated bi-antennary complex-type N-glycan. It has two branches and a fucose sugar attached to its core, but lacks sialic acid and galactose residues. Its molecular weight is approximately 1463.
This glycan is commonly found on mammalian glycoproteins, including human immunoglobulin G (IgG) antibodies, and is one of the most prevalent glycans attached to monoclonal antibodies, alongside G1F and G2F isomers. These N-glycans are attached to the asparagine 297 residue within the Fc region of IgG molecules. G0F is also a substructure of other bi-antennary N-linked oligosaccharides, such as A2F, A1F, and NA2F.
The Role of g0f Glycan in the Body
G0F glycan’s presence on proteins, particularly antibodies, influences their biological activities, impacting protein binding, solubility, and stability. These glycoforms also affect pharmacokinetics and pharmacodynamics.
G0F glycan plays a role in modulating immune system functions. The N-glycans attached to the Fc domain of IgG antibodies affect their effector functions, such as antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). These functions help the immune system clear pathogens and abnormal cells. Changes in IgG glycosylation patterns, including g0f levels, can alter the antibody’s affinity for Fc gamma receptors, influencing the immune response.
g0f Glycan and Human Health
Alterations in g0f glycan levels or structure are increasingly recognized as indicators and contributors to various human health conditions. In autoimmune diseases, where the immune system mistakenly attacks the body’s own tissues, specific glycan signatures, including those involving g0f, are observed on immune cells and serum proteins.
For instance, increased levels of agalactosylated IgG (which includes g0f) are a known feature in rheumatoid arthritis (RA) patients compared to healthy individuals. The quantities of g0f glycan have been shown to be statistically different in RA patients, with an average of 0.85 ± 0.34 in RA patients versus 0.61 ± 0.19 in healthy controls.
Changes in g0f glycan levels are also associated with inflammatory diseases. In inflammatory bowel disease (IBD), an increase in the ratio of agalactosylated to digalactosylated fucosylated glycans (G0F/G2F) has been correlated with active disease in both Crohn’s disease (CD) and ulcerative colitis (UC) patients. This suggests that the g0f/g2f ratio could serve as a promising biomarker for disease activity. The shift in IgG glycosylation towards more agalactosylated structures, like g0f, is often linked to a pro-inflammatory phenotype.
Furthermore, research indicates that altered g0f glycan patterns may be relevant in other conditions. For example, bevacizumab and adalimumab, two therapeutic monoclonal antibodies, show g0f as their predominant glycan, which may influence their interactions within the body. The study of g0f glycan and other glycoforms offers insights into disease mechanisms and holds potential for developing new diagnostic tools and therapeutic strategies.